An evaluation of the budget impact of a new 20% subcutaneous immunoglobulin (Ig20Gly) for the management of primary immunodeficiency diseases in Switzerland.

INTRODUCTION: While most individual primary immunodeficiency diseases (PID) are rare, the collective prevalence of PID results in a substantial economic and clinical burden. The aim of this study was to evaluate the budgetary implications of Ig20Gly (Immune Globulin Subcutaneous [human] 20% solution; CUVITRU ® , Baxalta US Inc, now part of Shire Plc, Westlake Village, CA, USA) as a treatment for PID relative to intravenous immunoglobulin (IVIG) and other subcutaneous immunoglobulin (SCIG) formulations in the Swiss health care setting. MATERIALS AND METHODS: A budget impact model was developed in Microsoft Excel to capture the estimated prevalence of PID in Switzerland, the proportion of patients treated in different health care settings, and the costs of administering SCIG and IVIG in each setting. Unit costs were based on a recent cost-minimization analysis of SCIG in Lausanne, and drug costs were taken from the Spezialitätenliste. All costs were reported in 2016 Swiss Francs (CHF), and future costs were not discounted. RESULTS: The total cost of treating PID in Switzerland was estimated to be CHF 11.16 m over 3 years, comprising CHF 9.28 m of drug costs and CHF 1.87 m of ancillary costs, including health care professional time and other administration costs, such as pumps and needle sets. The analysis showed that using Ig20Gly in place of other SCIG formulations would be cost neutral, while using Ig20Gly in place of IVIG would result in savings of 4.0%. CONCLUSION: Ig20Gly would be cost neutral relative to existing SCIG products and would result in cost savings relative to IVIG in patients with PID in Switzerland, even with modest uptake.

Burden of illness for super-refractory status epilepticus patients.

OBJECTIVE: To provide an estimate of the annual number of super-refractory status epilepticus (SRSE) cases in the US and to evaluate utilization of hospital resources by these patients. METHODS: The Premier Hospital Database was utilized to estimate the number of SRSE cases based on hospital discharges during 2012. Discharges were classified as SRSE cases based on an algorithm using seizure-related International Classification of Diseases-9 (ICD-9) codes, Intensive Care Unit (ICU) length of stay (LOS), and treatment protocols (e.g. benzodiazepines, anti-epileptic drugs (AEDs), and ventilator use). Secondary analyses were conducted using more restrictive algorithms for SRSE. RESULTS: A total of 6,325 hospital discharges were classified as SRSE cases from a total of 5,300,000 hospital discharges. Applying a weighting based on hospital characteristics and 2012 US demographics, this projected to an estimated 41,156 cases of SRSE in the US during 2012, an estimated incidence rate of ∼13/100,000 annually for SRSE in the US. Secondary analyses using stricter SRSE algorithms resulted in estimated incidence rates of ∼11/100,000 and 8/100,000 annually. The mean LOS for SRSE hospitalizations was 16.5 days (median =11; interquartile range [IQR] = 6-20), and the mean ICU LOS was 9.3 days (median =6; IQR =3-12). The mean cost of an SRSE hospitalization was $51,247 (median = $33,294; 95% CI = $49,634-$52,861). LIMITATIONS: The analysis uses ICD-9 diagnostic codes and claims information, and there are inherent limitations in any methodology based on treatment protocol, which created challenges in distinguishing with complete accuracy between SRSE, RSE, and SE on the basis of care patterns in the database. CONCLUSION: SRSE is associated with high mortality and morbidity, which place a high burden on healthcare resources. Projections based upon the findings of this study suggest an estimated 25,821-41,959 cases of SRSE may occur in the US each year, but more in-depth studies are required.

Variation in hospital resource use and cost among surgical procedures using topical absorbable hemostats.

BACKGROUND: Adjunctive hemostats are used to assist with the control of intraoperative bleeding. The most common types are flowables, gelatins, thrombins, and oxidized regenerated celluloses (ORCs). In the US, Surgicel(®) products are the only US Food and Drug Administration-approved ORCs. OBJECTIVE: To compare the outcomes of health care resource utilization (HRU) and costs associated with using ORCs compared to other adjunctive hemostats (OAHs are defined as flowables, gelatins, and topical thrombins) for surgical procedures in the US inpatient setting. PATIENTS AND METHODS: A retrospective, US-based cohort study was conducted using hospital inpatient discharges from the 2011-2012 calendar years in the Premier Healthcare Database. Patients with either an ORC or an OAH who underwent a cardiovascular procedure (valve surgery and/or coronary artery bypass graft surgery), carotid endarterectomy, cholecystectomy, or hysterectomy were included. Propensity score matching was used to create comparable groups of ORC and OAH patients. Clinical, economic, and HRU outcomes were compared. RESULTS: The propensity score matching created balanced patient cohorts for cardiovascular procedure (22,718 patients), carotid endarterectomy (10,890 patients), cholecystectomy (6,090 patients), and hysterectomy (9,348 patients). In all procedures, hemostatic agent costs were 28%-56% lower for ORCs, and mean hemostat units per discharge were 16%-41% lower for ORCs compared to OAHs. Length of stay and total procedure costs for patients treated with ORCs were lower for carotid endarterectomy patients (0.3 days and US$700) and for cholecystectomy patients (1 day and US$3,350) (all P<0.001). CONCLUSION: Costs and HRU for patients treated with ORCs were lower than or similar to patients treated with OAHs. Proper selection of the appropriate hemostatic agents has the potential to influence clinical outcomes and treatment costs.

Reduction in hospital costs and resource consumption associated with the use of advanced topical hemostats during inpatient procedures.

OBJECTIVE: The use of hemostatic agents has increased over time for all surgical procedures. The purpose of this study was to evaluate the newer topical absorbable hemostat products Surgicel * Fibrillar † and Surgicel SNoW ‡ (Surgicel advanced products, abbreviated as SAPs) compared to the older product Surgicel Original (SO) with respect to healthcare resource use and costs in procedures where these hemostats are most commonly used. RESEARCH DESIGN AND METHODS: A retrospective analysis of the Premier hospital database was used to identify adults who underwent brain/cerebral (BC), cardiovascular (CV: valve surgery and coronary artery bypass graft) and carotid endarterectomy (CEA) between January 2011-December 2012. Among these patients, those treated with SAPs were compared to those treated with SO. Propensity score matching (PSM) was used to create comparable groups to evaluate differences between SAPs and SO. MAIN OUTCOME MEASURES: The primary end-points for this study were length of stay (LOS), all-cause total cost, number of intensive care unit (ICU) days, ICU cost, transfusion costs and units, and SO/SAP product units per discharge. RESULTS: Matched PSM created patient cohorts for SO and SAPs were created for BC (n = 758 for both groups), CV (n = 3388 for both groups), and CEA (n = 2041 for both groups) procedures. Patients that received SAPs had a 14-16% lower mean LOS for each procedure compared to SO, as well as 12-18% lower total mean cost per discharge for each procedure (p < 0.02 for all results). Mean ICU costs for SAPs were also lower, with a reduction of 20% for BC and 19% for CV compared to SO (p < 0.01). However, for CEA, there was no statistically significant difference in ICU costs for SAPs compared to SO. CONCLUSIONS: In a retrospective hospital database analysis, the use of SAPs were associated with lower healthcare resource utilization and costs compared to SO.

Cost-effectiveness of bronchial thermoplasty in commercially-insured patients with poorly controlled, severe, persistent asthma.

OBJECTIVES: We examined the cost-effectiveness of treating poorly controlled, severe, persistent asthma patients with bronchial thermoplasty (BT), a novel technology that uses thermal energy to reduce airway smooth muscle mass, with 5-year outcome data demonstrating a durable reduction in asthma exacerbations. STUDY DESIGN: We conducted a model-based cost-effectiveness analysis assessing 5-year healthcare utilization, patient quality of life and adverse events. METHODS: We utilized Markov modeling to estimate the costs and quality-of-life impact of BT compared with high-dose combination therapy among poorly controlled, severe, persistent asthma patients: those requiring high-dose combination therapy and having experienced an asthma exacerbation-related ER visit in the past year. RESULTS: The cost-effectiveness of BT was US$5495 per quality-adjusted life year; and approximately 22% of sensitivity analysis iterations estimated BT to reduce costs and increase quality of life. CONCLUSIONS: BT is a cost-effective treatment option for patients with poorly controlled, severe, persistent asthma.

Management patterns of medicare patients undergoing treatment for upper urinary tract calculi.

PURPOSE: We conducted this study to identify differences in the re-treatment rates and ancillary procedures for the two most commonly utilized stone treatment procedures in the Medicare population: ureteroscopy (URS) and shock wave lithotripsy (SWL). MATERIALS AND METHODS: A retrospective claims analysis of the Medicare standard analytical file 5% sample was conducted to identify patients with a new diagnosis of urolithiasis undergoing treatment with URS or SWL from 2009-2010. Outcomes evaluated: (1) repeat stone removal procedures within 120 days post index procedure, (2) stent placement procedures on the index date, 30 days prior to and 120 days post index date, and (3) use of general anesthesia. RESULTS: We identified 3885 eligible patients, of which 2165 (56%) underwent SWL and 1720 (44%) underwent URS. Overall, SWL patients were 1.73 times more likely to undergo at least one repeat procedure than URS patients, and twice as likely to require multiple re-treatments compared to URS. Among those with ureteral stones, SWL patients were 2.27 times more likely to undergo repeat procedures. The difference was not statistically significant in renal stone patients. Overall, SWL patients were 1.41 times more likely than URS patients to have a stent placed prior to index procedure, and 1.33 times more likely to have a stent placed subsequent to the index procedure. The majority of URS patients (77.8%) had a stent placed at the time of index procedure. There was no significant difference in anesthetic approaches between SWL and URS. CONCLUSIONS: Patients undergoing SWL are significantly more likely to require re-treatments than URS patients. SWL patients are also significantly more likely to require ureteral stent placement as a separate event. SWL and URS patients have similar rates of general anesthesia.

Economic outcomes of treatment for ureteral and renal stones: a systematic literature review.

PURPOSE: We evaluated the cost-effectiveness of ureteral/renal stone treatment by comparing ureteroscopy, extracorporeal shock wave lithotripsy and percutaneous nephrolithotomy. MATERIALS AND METHODS: We performed a systematic literature search to identify studies of treatment for adults with ureteral and renal stones that were published between 1995 and 2010. For inclusion in analysis studies had to provide the stone-free rate and the cost of at least 2 therapies. RESULTS: Ten studies were identified, including 8 with an observational design and 2 that synthesized data using decision modeling techniques. Five of 6 studies, including 1 of 2 from the United States, compared ureteroscopy vs shock wave lithotripsy for proximal stones and showed a higher stone-free rate and lower cost for ureteroscopy. Four of the 5 studies, including the only American study, compared ureteroscopy vs shock wave lithotripsy for distal ureteral stones and also showed such an economically dominant result. Studies of shock wave lithotripsy vs percutaneous nephrolithotomy and ureteroscopy vs percutaneous nephrolithotomy for renal stones demonstrated higher cost and a higher stone-free rate for percutaneous nephrolithotomy. CONCLUSIONS: Despite the great heterogeneity and limited quality of available cost-effectiveness evaluations most studies demonstrated that ureteroscopy was more favorable than shock wave lithotripsy for ureteral stones in stone-free rate and cost.

Risk-sharing arrangements that link payment for drugs to health outcomes are proving hard to implement.

Risk-sharing agreements, under which payers and pharmaceutical manufacturers agree to link payment for drugs to health outcomes achieved, rather than the volume of products used, offer an appealing payment model for pharmaceuticals. Although such agreements have been widely touted, the experience to date mainly demonstrates how hard they are to implement. Barriers include high implementation costs, measurement challenges, and the absence of a suitable data infrastructure. Risk-sharing arrangements could gain traction in the United States as payers and product manufacturers acquire experience with the concept and as measurement techniques and information systems improve. For the foreseeable future, they are likely to remain the exception as drug companies pursue payment models unconnected to data collection or performance assessment.

A policy model to evaluate the benefits, risks and costs of warfarin pharmacogenomic testing.

BACKGROUND: In 2007, the US FDA added information about pharmacogenomics to the warfarin label based on the influence of the CYP2C9 and VKORC1 genes on anticoagulation-related outcomes. Payers will be facing increasing demand for coverage decisions regarding this technology, but the potential clinical and economic impacts of testing are not clear. OBJECTIVE: To develop a policy model to evaluate the potential outcomes of warfarin pharmacogenomic testing based on the most recently available data. METHODS: A decision-analytic Markov model was developed to assess the addition of genetic testing to anticoagulation clinic standard care for a hypothetical cohort of warfarin patients. The model was based on anticoagulation status (international normalized ratio), a common outcome measure in clinical trials that captures both the benefits and risks of warfarin therapy. Initial estimates of testing effects were derived from a recently completed randomized controlled trial (n = 200). Healthcare cost ($US, year 2007 values) and health-state utility data were obtained from the literature. The perspective was that of a US third-party payer. Probabilistic and one-way sensitivity analyses were performed to explore the range of plausible results. RESULTS: The policy model included thromboembolic events (TEs) and bleeding events and was populated by data from the COUMAGEN trial. The rate of bleeding calculated for standard care approximated bleeding rates found in an independent cohort of warfarin patients. According to our model, pharmacogenomic testing provided an absolute reduction in the incidence of bleeds of 0.17%, but an absolute increase in the incidence of TEs of 0.03%. The improvement in QALYs was small, 0.003, with an increase in total cost of $US162 (year 2007 values). The incremental cost-effectiveness ratio (ICER) ranged from testing dominating to standard care dominating, and the ICER was <$US50,000 per QALY in 46% of simulations. Results were most sensitive to the cost of genotyping and the effect of genotyping. CONCLUSION: Our model, based on initial clinical studies to date, suggests that warfarin pharmacogenomic testing may provide a small clinical benefit with significant uncertainty in economic value. Given the uncertainty in the analysis, further updates will be important as additional clinical data become available.

The adoption of cost-effectiveness acceptability curves in cost-utility analyses.

BACKGROUND: Cost-effectiveness acceptability curves (CEACs) plot the probability that one health intervention is more cost-effective than alternatives, as a function of societal willingness to pay for additional units of health (e.g., life-years or quality-adjusted life-years gained). OBJECTIVES: To quantify the adoption of CEACs in published cost-utility analyses (CUAs), and to identify factors associated with CEAC use. METHODS: Data from the Tufts Medical Center Cost-Effectiveness Analysis Registry (www.cearegistry.org), a database with detailed information on approximately 1,400 CUAs published in the peer reviewed literature through 2006, was analyzed. The registry includes data on study origin, study methodology, reporting of results, whether CEACs were presented, and a subjective quality score. Univariate and multivariate logistic regression analyses were used to identify factors predicting CEAC use, from their introduction in 1994 through 2006. RESULTS: Approximately 15% of CUAs published since 1994 present a CEAC. The use of CEACs has increased rapidly in recent years, from 2.1% of published CUAs in 2001 to 32.6% in 2006 (P < 0.0001). The most significant predictors of CEAC use were study quality (odds ratio [OR]: 2.26; 95% confidence interval [CI]: 1.80, 2.85), recent publication (OR: 1.99; 95% CI: 1.73, 2.29), and whether studies pertain to the UK (OR: 5.66; 95% CI: 3.67, 8.72) or Sweden (OR: 3.76; 95% CI: 1.67, 8.44). CONCLUSIONS: CEAC use is increasing in the published cost-effectiveness literature, especially in UK-based studies.

Personalized medicine: factors influencing reimbursement.

OBJECTIVES: Personalized medicine (PM) has attracted tremendous interest, but yielded few marketed products. We examined factors influencing the reimbursement of existing PM technologies. METHODS: We conducted six case studies of the following paired genetic tests and treatments: HER2/neu with trastuzumab (Herceptin); hepatitis C genotyping with ribavirin/pegylated interferon; Oncotype DX with chemotherapy; UGT1A1 with irinotecan (Camptosar); VKORC1/CYP2C9 with warfarin; BRCA1/2 with prophylactic surgical measures; and Oncotype DX with chemotherapy. We developed a framework for categorizing PM technology, and assessed factors influencing reimbursement, including quality of evidence, type of regulatory oversight, presence of clinical guidelines, and cost-effectiveness. RESULTS: PM is not a monolithic concept, but rather encompasses different types of technology. The strength of evidence available for existing PM technology varies widely and, along with endorsement of clinical guidelines, appears to be the strongest predictor of reimbursement. In the absence of reimbursement, direct-to-consumer marketing has continued for some PM technology. The type of regulatory oversight and the results of cost-effectiveness analysis do not appear to be associated with reimbursement to date. CONCLUSIONS: To date, the promise and hype of PM has outpaced its evidentiary support. In order to achieve favorable coverage and reimbursement and to support premium prices for PM, manufacturers will need to bring better clinical evidence to the marketplace and better establish the value of their products.

A review of public policy issues in promoting the development and commercialization of pharmacogenomic applications: challenges and implications.

This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy and informed consent. Challenging technical, business, and policy-related issues might either hinder progress in the field of pharmacogenomics or potentially accelerate it, depending on how they are addressed and resolved. How well the numerous important stakeholders - both private and public - address these issues will be critical for pharmacogenomics to deliver on its promise.

Modelling costs and outcomes of expanded availability of emergency contraceptive use in British Columbia.

BACKGROUND: Emergency contraception (EC) can potentially reduce unwanted pregnancies and abortions. However, these agents are underused due to lack of awareness and barriers to utilization. While earlier economic evaluations have indicated that use of EC is potentially cost-effective, recent evidence of a lower risk of pregnancy following unprotected intercourse than previously reported suggest prior studies may have over-estimated cost savings. OBJECTIVES: To model cost savings and pregnancy-related outcomes associated with the policy change authorizing pharmacist provision of EC in British Columbia, and to estimate the costs of initiatives to further women's awareness and utilization of EC that would result. METHODS: Three decision analytic models were developed evaluating current EC utilization (physician-only), EC utilization following pharmacist provision and potential expanded EC awareness and utilization following a public awareness initiative. Models were developed from the Ministry of Health perspective for 2001 using cost and event data from the Ministry supplemented by data from the literature. RESULTS: Current EC utilization saved the Ministry $2.20 million (95% CR: $0.15 million, $4.90 million) in medical costs the first year, and incremental savings from pharmacist provision was $0.64 million (95% CR: $0.24 million, $1.28 million). A public awareness initiative costing less than $2.57 million (95% CR: $0.22 million, $5.75 million) annually is potentially cost saving. CONCLUSIONS: Pharmacist provision of EC was cost saving to the Ministry, even when the estimated risk of pregnancy in the population is less than assumed in previous studies. Increasing EC availability directly from pharmacists and increasing EC awareness have the potential to reduce health care costs.

Screening for the alpha-adducin Gly460Trp variant in hypertensive patients: a cost-effectiveness analysis.

BACKGROUND: Studies have shown that approximately 80% of hypertensive patients do not take diuretics despite their recommendation as a first-line therapy. A recent study reported that hypertensive patients with the Gly460Trp variant in the alpha-adducin gene are more likely to benefit from diuretic therapy. The objective of this study was to evaluate the potential cost effectiveness of screening for the alpha-adducin Gly460Trp variant among hypertensive patients. METHODS: A decision analytic Markov model was developed to estimate the clinical and economic outcomes comparing screening for the Gly460Trp variant to identify patients for addition of a diuretic compared to no screening and no addition of diuretic (usual care) in a hypothetical cohort of treated hypertensive patients not receiving diuretic therapy. We used a lifetime horizon and payer perspective. Cost, utility and epidemiological data were obtained from the literature. One-way, probabilistic, and scenario sensitivity analyses were conducted to evaluate the uncertainty in the results. RESULTS: The screening strategy increased quality adjusted life years (QALYs) by 0.14 (95% confidence range [CR]: 0.05, 0.36) and saved dollar 1834 (dollar 505, dollar 5174) compared to usual care. The most influential input was the strength of the interaction between the alpha-adducin gene variant and diuretic effect. CONCLUSIONS: Our results suggest that screening for the alpha-adducin gene variant may be a useful mechanism to identify patients most likely to benefit from diuretic therapy and improve compliance with current treatment guidelines.